SEEING THE LIGHT: INHERENT TARGETING WINS $2.25M SBIR GRANT

Transcript

Every year in the US, roughly 40 million operations are performed, which cause about 600,000 nerve injuries for patients, some leading to permanent disability (https://reporter.nih.gov/project-details/10081607). Connor Barth, PhD, co-founder of Inherent Targeting in Portland, Oregon, wants to do something about it. So he turned to us.

Thanks in part to ScienceDocs, in March 2021 Inherent Targeting received its first SBIR grant, an NIH Fast-Track Phase I and Phase II grant of $2.25M, to facilitate the clinical translation of a novel fluorescence-guided surgery (FGS) technology.

Claire Sykes, ScienceDocs Science Writer and Interviewer, talked via Zoom with Dr. Barth on April 21, 2021 about this exciting technology and where Inherent Targeting is headed. You can watch that interview here, and below is the edited transcript of it.

Claire Sykes:  When I was reading up on you I got really inspired, going further and further into the net, and I came up with three things that seemingly don’t have anything in common, and “Why is she going to mention these?” but: 22 Golden Gate Bridges, 543 football fields and nearly seven Mount Everests. Each of those comes to 37 miles—the number of miles that our nerves travel in our human bodies. So what I want to know is, what does all that have to do with Inherent Targeting?

Connor Barth: What we’re trying to do is enable surgeons to actually visualize the nerves during surgery, so they can get a surgical roadmap if you will, to guide their surgical decision-making and improve outcomes for patients.

Claire Sykes:  Well, because anybody going into surgery, one of the many things they think about is, “Oh my God, I hope they don’t cut a nerve. I hope a nerve doesn’t get cut or twisted or somehow damaged.”

Connor Barth:  Yeah, so nerves are damaged a lot during surgery; that’s a common surgical problem. And it’s a big fear for patients, as well as surgeons. There are a lot of efforts taken to try to spare people’s nerves, but some of the efforts are in vain because it’s just so hard to see the nerves. It can be as simple as a hernia repair, a very common procedure, where the nerves can be entrapped by the sutures that are used to stitch up the hernia. Or as complicated as a thyroidectomy or other head and neck surgeries where you have a lot of complicated structures that you’re working around, trying to resect either cancer or different disease tissues, and the nerves can be easily damaged because they are very fragile and can be stretched or burned or cut or any number of things. So being able to see the nerves and monitor their health throughout the surgery would be really helpful for surgeons.

Claire Sykes: You’re using what’s called fluorescence-guided surgery technology. I love the video on your website, www.inherenttargeting.com. Your website’s beautiful, by the way. Anyway, so I watched this thing and I see what looks like lobster pincers going at it on this fleshy, pulpy mass of nerves going every which way and I’m thinking, “I hope this surgeon knows what they’re doing, because look at all those little lines.” The surgeon is just using the naked eye or knowledge of anatomy to tell what’s going on. But then the next shot is sort of this film noir, black-and-white of a midnight highway, the visible nerve a solid white line. It’s very contrasted, very stark, the difference—and memorable. It’s wonderful technology, which your website says will “Save Time. Improve Outcomes. Reduce Costs.”

So, you’ve devoted your career and your life and your days to the study of nerves and you’re a biomedical engineer. What is it about the nervous system for you? What excites you about it?

Connor Barth:  ell, I got into this field because I really liked developing new imaging technologies and this was such a nice hands-on approach to improving patient care. When you think of medical imaging, you see a lot of MRIs or CT scans, whole-body kind of imaging, that’s usually done preoperatively. What we’re trying to do is take that same principle and apply it to real-time imaging in the surgical field. That’s what fluorescence-guided surgery can do.

What I quickly identified was that a lot of the research in the field, and development, has been focused on cancer-targeted fluorescence-guided surgery, which has a great deal of benefit. You can improve cancer resection and help save people’s lives. But it seemed there wasn’t a lot of work that had been done in helping surgeons preserve the normal anatomy, the nerves or the blood vessels. So that was something that I was interested in, in developing that space, because there was obviously this need for that. And that’s where I’ve started to devote all our time—improving nerve preservation during surgery. Then, as I got into that, I realized the nervous system is extremely important for all sorts of functions, as well as feeling, and quality of life after surgery. So it started to make a lot of sense why this is a good problem to go after, and very important for patient outcomes post-surgery.

Claire Sykes: You were working as a post-doc at OHSU with Dr. Summer Gibbs [biomedical engineer]. Can you tell us how you got there and what you discovered in working with her? What were some big moments there in that lab? Because from there, you formed the company, in 2019, and got the grant, which we’ll get to later. Big news item here.

Connor Barth: Yeah. So I joined the lab as a graduate student back in 2014 with this idea I wanted to study imaging and become a biomedical engineer, and started out as a PhD student in the [Gibbs Laboratory] with Summer Gibbs there. She was doing a lot of really cool research with image-guided surgery, and I started out taking that idea of identifying nerves during surgery with this technology and developing the different ways that it can be administered. You can either inject it into the patient and view the nerves in the body, or you can apply it topically, sort of painted onto the surgical field. So we developed those ways of doing it.

And then another member joined the lab, Lei Wang. He is our expert, organic chemist and the breakthrough we had was when we [combined] all of our expertise together. Lei did a lot of great synthesis, and developed the library of compounds that could be promising, and then we screened those and had a breakthrough where we identified a compound that was ready for clinical translation, ready for use in humans. That was the point where we were like, okay, let’s spin out a company. So that’s the story of how we got to where we are. And we’re going to keep on going and see where we can take it.

Claire Sykes:  You’ve got many miles to go. At least 37. So why did you decide to call it Inherent targeting?

Connor Barth:  Our technology is based on small-molecule fluorophores, and the nerve-targeting piece of the molecule that allows for seeing nerve specificity is fluorophore, itself, and technically that’s called structure-inherent targeting. The idea there is that we’re taking these fluorescent reporter molecules and using them both as the targeting agent and the imaging agent, which is not typically done in this field. Typically, you have a targeting agent like a drug or an antibody and you tag a fluorophore to that.

Claire Sykes:  What exactly are fluorophores?

Connor Barth:  These are chemicals basically, small-molecule drugs that when you shine a certain wavelength of light onto them, they emit fluorescence that you can pick up with the camera. It takes a certain type of molecule to do so, but luckily Lei, our chemist, is very experienced with developing and creating these kinds of compounds and we were able to create compounds that were both nerve-specific and had the right fluorescent property, all in one package. And that’s where we got the name Inherent Targeting.

Claire Sykes: From what I read, the technology uses near-infrared light.

Connor Barth: The near-infrared fluorescence was kind of the breakthrough we had. It allows you to identify the nerves buried beneath several layers of tissue and visualize, highlight nerves that you wouldn’t be able to see with your naked eye, because you can actually see buried tissue, and with high resolution. There are several benefits to that, so that was major.

Claire Sykes:  So what challenges, what bumps in the road have you faced along the way and how have you dealt with them?

Connor Barth:  The biggest challenge generally has been coming from my education as a PhD scientist to becoming a successful leader, an entrepreneur of a small biotech company, because it’s totally different—business and marketing and sales and all that kind of thing that I never had to learn about. So I’ve been having to teach myself as I go. What’s been really helpful has been reaching out to the community, both at OHSU, the resources that are available there, and locally, as well as through our network connections that have experience with this kind of thing, getting their input, feedback, advice. The tech transfer office and the Office of Collaborations and Entrepreneurship at OHSU were helpful at the beginning to show us opportunities for training, as well as help with our business plan, or commercialization plan. And then us reaching out to other consultants or advisors, who have helped to answer a lot of questions we’ve had and teach our team how to run a successful biotech start-up.

Claire Sykes:  Yeah, because it’s a business, and you’re used to being in a lab. This is a whole other game. So who have been some of your mentors?

Connor Barth:  We worked closely with OHSU to begin with, and the tech transfer advisor there, Anne Carlson, has been helpful in getting the IP [intellectual property] all figured out, the patents and everything, and then finding opportunities for us. As part of that, we’ve also worked with Lisa Lukaesko, with the Office of Collaborations and Entrepreneurship. She was helpful to come in and, from the business side of things, set up the commercialization plan, our executive summary, things that we can then send out to investors. And then we’ve also worked with one of the entrepreneurs-in-residence at OHSU, David Katz [biomedical engineer], and he’s now an advisor for our company. He’s another founder of a biotech company in Portland [Sparrow Pharmaceuticals], and he has a lot of experience with clinical studies and this kind of clinical translation that we’re trying to achieve. There are many, many others that have been helpful, both from our academic connections at other universities, as well as in the field of fluorescence-guided surgery. We’re talking with these folks who have experience with the industry and with translation of novel technologies.

Claire Sykes: You are so well connected. That must feel so supportive and strengthening for you to have all of those people and resources with you, and Portland’s a great city for that.

Connor Barth:  Yeah. They’re very helpful as far as the community in Portland. They all seem to be very excited about new ventures and wanting to help. I should also mention we’re part of the Oregon Bioscience Incubator and those resources have been really helpful to us, as well, and that community.

Claire Sykes:  It’s a strong one.

Connor Barth: Yeah.

Claire Sykes:  So you applied for an NIH grant and you got the Fast-Track SBIR. Congratulations! I mean whoa, that’s quite the award to get. It’s a $2.25 million grant. So what did they see in you? How did you make this happen?

Connor Barth: As I mentioned, when we first started out, we were scientists that didn’t know the business side, but we knew that we needed to get funding. So our first effort was to look at grants because that’s something we’re familiar with, coming from the academic. So we started writing grant applications and our first submission didn’t get scored. We realized, okay, we need to take it back to the drawing board and try again, and revamp things and learn about business and all of the commercialization-plan side of things. So that’s one thing with this bigger grant. We needed to submit a long commercialization plan outlining all of our goals as a business and how we’ll get to them.

We got some pilot-grant funding from Business Oregon to work with ScienceDocs, who helped us write our resubmission of the [NIH] grant. ScienceDocs helped with getting that commercialization-plan piece nailed down and formatted in the right way, because it was tough to know the exact format we needed to do. But with the experience of ScienceDocs and the help of Gage Greening [biomedical engineer], who was our consultant who worked with us, we were able to get a pretty solid commercialization plan together, and that paired well with our science piece of it. That really helped us because the next submission, they liked it and they gave us a good score and that is what ended up getting funded here.

Claire Sykes: Smart move. In running any business, there are things you can farm out, definitely.

Connor Barth: Something I’ve learned is that using those resources, assistance that’s available and people like ScienceDocs or other consultants, it can be valuable and extremely worthwhile to do so. The investment there paid off, for sure.

Claire Sykes:  What is your next step?

Connor Barth: I’ve been pretty busy administratively, getting everything ready, now that we have funding to build the company and get going on the development. Our first goal is to take the compounds that we identified as having potential for clinical translation and complete the selection of a final lead compound. Once it goes through clinical translation, the remainder of the grant is there to fund the preclinical testing that’s needed, safety testing needed to start, first, in human clinical trials. So hopefully by the end of this grant cycle, which is a two-year grant cycle, we’ll have the data needed, and the proven safety and pharmacology needed, to take our technology to humans. Right now, I’m doing both of that, development as well as looking ahead, and thinking about the next step and about raising money for clinical trials that we can run in patients. That’s going to be I think the most exciting time, once we can start testing in humans and showing that it’s going to help them in surgery.

Claire Sykes: In every surgical procedure. It’s so necessary, and so great to hear that you’re doing this. What do you want people, laypeople, to know about Inherent Targeting? What is useful to know for people who are not biomedical engineers or otherwise technologically oriented?

Connor Barth: I guess I would just say our ultimate vision is to enable surgeons to “cut by color,” that this technology exists. It’s in clinical translation; it’s not FDA- approved yet, but there are a number of these technologies out there, and I think it would be great for the common man to understand they’re there and that there’s possibility. Our ultimate vision is that you’re going to be able to flip a switch in the operating room and then everything that’s important is going to light up and the surgeon’s going to have a clear path to their surgery.

That’s going to make it just so much easier for them, and make surgical outcomes so much better so that patients can experience less loss of function or pain from nerve damage. Or, in the future, we may even take some of the technology we’re developing for tumor targeting and combine these uses together so you can identify cancer and nerves at the same time, and get better resection on your cancer while also preserving nerves. We’re anticipating that ability to give a clear picture of surgery, as it’s happening, and enable more precise surgery.

Claire Sykes: Whether it’s robotic surgery or traditional. So I tend to do this when I get into the sciences because I’m not a scientist, but it’s so inspiring for me, and so one thing that I thought of was, gosh there are these 37 miles traveling around in us, and if those 37 miles was music—because music affects the nervous system, music has an effect on the brain—if the nervous system was music, and I’m thinking of your passion for it, your interest in it, your devotion to it, given that, those two together, what kind of music would you hear, Connor?

Connor Barth:  Yeah, this is interesting because one of my main interests, hobbies, is music and I’m really into electronic music, so I would say it’d probably be something like that, where you’d be hearing different, almost synthesized kinds of signals coming in and out. For me, what I like about that kind of music is that it’s very dance-oriented. So that’s something I think—dancing, involving yourself with music, you’re stimulating your nervous system along with the music and you’re in tune with it as a person, almost putting your entire nervous system in tune with the music. So I think something like that would be kind of what I would hear.

Claire Sykes:  Oh, I love that answer because it also seems to fit with your profession. Of course you would be into electronic music. There’s a musical engineer somewhere in you. That’s so great.

Well, I just think it’s wonderful, the work that all three of you are doing with Inherent Targeting and I’m excited for you, we all are, and I wish you the very best with it. And I just have one final question and that is, What are you going to do today about it? What are you going to do that’s going to continue to feed your passion?

Connor Barth:   I think right now we’re in the process of some pretty incredible growth and so I’m trying to take it in while I go through it. But I think, for me, being able to look back at the accomplishments we’ve made and then take that as motivation going forward—that’s powerful. One thing that we just recently did that drives me is when we see the results from the studies we’re doing. We’ll do studies testing the fluorophore with different nerve models, and when it works, like most of the time, when I see this, I’m like, this is amazing, we need this for patients. Every time I see that new picture of the nerve and it’s really clear and high contrast, it motivates me all over again. Just yesterday we did some studies and saw some cool images of cranial nerves, which are often injured during skull-based tumor resection and they’re all weak, and the majority of time, there’s some nerve complications. And it’s like, this is great. It’s really motivating.

Claire Sykes:  A lot to dance to.

Connor Barth:  Yeah, for sure.

Claire Sykes:  Oh gosh, thank you so much for telling us your story.  I feel optimistic and hopeful with the work that you’re doing, and it’s such good work and so needed and it’s going to make a huge difference for many, many people. There’s going to be a huge impact with what you’re doing. I thank you for that.

Connor Barth:  Thanks. We’re excited to see the progress and see where we can take it.

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